The development of cardiac hypertrophy in response to a sustained stress provides a basic compensatory mechanism for the heart, allowing it to meet the demands of an increased work load. Although initially beneficial in terms of maintaining total pump performance, the development of cardiac hypertrophy may result in a depression of the intrinsic contractile state of each individual unit of myocardium, which, if progressive, may eventuate in circulatory decompensation and heart failure. A critical, though unanswered question, is the extent to which hypertrophy once attained can undergo regression if the imposed stress is removed. The spontaneously hypertensive rat (SHR) provides a useful experimental model for longitudinal studies of the natural progression of pressure load ventricular hypertrophy. The present series of studies is designed to characterize the relationships between ventricular mass, geometry, performance, developed stress and oxygen consumption during the natural development of left ventricular hypertrophy in the SHR. Studies involving chronic antihypertensive therapy to interrupt the hypertensive disease process will be utilized to determine if effective control of arterial pressure can prevent, abate or reverse the hypertrophic process; also, it is planned to determine whether hypertrophy and the treatment of hypertension alter the function of the intact left ventricle as well as the isolated perfused left ventricle. The measurement of myocardial oxygen consumption in the isolated hearts will provide information concerning the effects of hypertension, hypertrophy and its treatment on the relation between myocardial performance and oxygen consumption. An important goal of the characterization of hypertrophy and the determinants of its reversibility is the identification of the factors which may be used in the timing of operations in patients with cardiac hypertrophy secondary to valvular lesions, and which will influence the outcome of the procedure.